Interleukin 1β and tumour necrosis factor α Inhibit acid secretion in cultured rabbit parietal cells by multiple pathways

被引:230
作者
Beales, ILP [1 ]
Calam, J [1 ]
机构
[1] Hammersmith Hosp, Royal Postgrad Med Sch, Dept Gastroenterol, London W12 0NN, England
关键词
acid secretion; aminopyrine; cytokines; interleukin; 1; beta; tumour necrosis factor alpha; parietal cell;
D O I
10.1136/gut.42.2.227
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background-The cytokines interleukin 1 beta (IL-1 beta) and tumour necrosis factor alpha (TNF-alpha) are inhibitors of gastric acid secretion when administered systematically. Aims-To investigate the inhibitory effect of IL-1 beta and TNF-alpha on cultured, acid secreting parietal cells in order to determine the mechanism of this inhibition. Methods-Rabbit parietal. cells were prepared by collagenase-EDTA digestion and counter flow elutriation. Acid secretory activity was assessed by aminopyrine accumulation, Results-IL-1 beta and TNF-alpha inhibited basal and stimulated acid secretion in a dose dependent manner; near maximal effects were seen with both at 10 ng/ml. Inhibition was maximal with 15 minutes pretreatment but seen with up to 18 hours of preincubation. Both cytokines inhibited histamine, carbachol, gastrin, forskolin, and A23187 stimulated acid secretion but had no effect on stimulation by dibutyryl-cAMP. inhibition of acid secretion was not accompanied by a change in radioligand binding to histamine H-2 or gastrin/CCKB receptors. Pertussis toxin abolished the inhibitory effects on histamine and forskolin stimulation. The tyrosine kinase inhibitor herbimycin reduced the inhibitory effects of TNF-alpha against all stimuli but only reduced the effects of IL-1 beta against histamine and forskolin stimulation. Conclusions-IL-1 beta and TNF-alpha seem to inhibit parietal cell acid secretion by multiple pathways; the inhibition occurs at postreceptor level and involves pertussis toxin and tyrosine kinase dependent and independent pathways. Mucosal production of cytokines may be important in the regulation of gastric acid secretion.
引用
收藏
页码:227 / 234
页数:8
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